Drug eluting surgical screw

ABSTRACT

The present invention provides a drug eluting surgical screw and a method for manufacturing a drug eluting surgical screw. The drug eluting surgical screw may include a shaft having a threaded portion, a head having a drive recess disposed at a proximal end of the shaft, the drive recess having a reservoir region and a driver engagement region, and at least one or more drug eluting components disposed within the reservoir region of the drive recess in a manner that does not substantially impair a connection between a driver and the surgical screw when the driver is operably disposed within the driver engagement region, each of the at least one or more drug eluting components including a carrier matrix and a therapeutic agent, the therapeutic agent being at least 20 wt % of the drug eluting component prior to any implantation of the drug eluting surgical screw.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional PatentApplication No. 61/683,262 entitled “Drug Eluting Surgical Screw”, filedAug. 15, 2012, which is incorporated herein by reference in itsentirety.

BACKGROUND OF INVENTION

The risks of infection following surgery are well documented. Thepresence of a foreign object such as a fracture fixation plate (e.g., anorthopedic fracture fixation plate) in the wound site may increase therisk of infection following surgery by providing a substrate forbacteria to adhere and proliferate, form a biofilm, and evade the hostimmune system. The risk of infection may increase in the case of openfractures where bacterial contamination of the wound prior to surgery iscommon. The consequences of implant related infection can besignificant, with recurring infection leading to chronic osteomyelitis,impaired healing, and potentially limb amputation. Antibiotic elutingimplants have been developed to address this concern.

SUMMARY OF THE INVENTION

One embodiment of the present invention is a drug eluting surgical screwincluding a shaft having a threaded portion; a head having a driverecess disposed at a proximal end of the shaft, the drive recess havinga reservoir region and a driver engagement region; and at least one ormore drug eluting components disposed within the reservoir region of thedrive recess in a manner that does not substantially impair a connectionbetween a driver and the surgical screw when the driver is operablydisposed within the driver engagement region, each of the at least oneor more drug eluting components including a carrier matrix and atherapeutic agent, the therapeutic agent being at least about 20 wt % ofthe drug eluting component prior to any implantation of the drug elutingsurgical screw.

In one embodiment, at least one of the at least one or more drug elutingcomponents is configured to elute at least about 80% of its therapeuticagent over a three day period starting from when the drug elutingsurgical screw is implanted into an animal.

In one embodiment, the concentration of the therapeutic agent of atleast one of the at least one or more drug eluting components is betweenabout 20 wt % and about 60 wt % of the at least one of the at least oneor more drug eluting components prior to any implantation of the drugeluting surgical screw.

In one embodiment, the concentration of the therapeutic agent of atleast one of the at least one or more drug eluting components is betweenabout 20 wt % and about 40 wt % of the at least one of the at least oneor more drug eluting components prior to any implantation of the drugeluting surgical screw.

In one embodiment, the reservoir region defines a reservoir volume, thedrive recess defines a drive recess volume and the reservoir volume isfrom about 10% to about 12% of the drive recess volume. In oneembodiment, the reservoir region of the drive recess is adjacent to thedriver engagement region and the at least one or more drug elutingcomponents do not extend into the driver engagement region. In oneembodiment, the carrier matrix of at least one of the at least one ormore drug eluting components includes a bioabsorbable polymer. In oneembodiment, the bioabsorbable polymer includes polycaprolactone,polylactic acid, polyglycolic acid, polyethylene glycol, or acombination thereof. In another embodiment, the carrier matrix of atleast one of the at least one or more drug eluting components includespolyethylene glycol, polyvinyl alcohol, glycerine, salts or a watersoluble crystalline solid. In another embodiment, the carrier matrix ofat least one of the at least one or more drug eluting componentsincludes silica, hydroxyapatite, calcium phosphate, bioglass or acombination thereof. In another embodiment, the carrier matrix of atleast one of the at least one or more drug eluting components includes ahydrophobic bioabsorbable polymer. In one embodiment, the hydrophobicbioabsorbable polymer includes a water swellable additive which swellswith water after implantation into the body. In one embodiment, thecarrier matrix of at least one of the at least one or more drug elutingcomponents includes a nonabsorbable polymer. In one embodiment, thenonabsorbable polymer includes poly(methyl methacrylate). In oneembodiment, the carrier matrix of at least one of the at least one ormore drug eluting components includes a nonabsorbable polymer and abioabsorbable polymer. In one embodiment, the bioabsorbable polymerincludes polycaprolactone, polylactic acid, polyglycolic acid,polyethylene glycol, or a combination thereof. In one embodiment, thebioabsorbable polymer of at least one of the at least one or more drugeluting components includes an erodible ceramic. In one embodiment, thebioabsorbable polymer of at least one of the at least one or more drugeluting components includes a biostable ceramic. In one embodiment, thebioabsorbable polymer of at least one of the at least one or more drugeluting components includes a natural biopolymer. In one embodiment, thenatural biopolymer includes gelatin, alginates, chitosan, collagen orhyaluronate.

In one embodiment, at least one of the one or more drug elutingcomponents includes a nonabsorbable polymer and a soluble additive. Inanother embodiment, the nonabsorbable polymer includes poly(methylmethacrylate). In another embodiment, the soluble additive includespolyethylene glycol, polyvinyl alcohol, glycerine, salts or a watersoluble crystalline solid.

In one embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes a concentration gradient.

In one embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes gentamicin. In anotherembodiment, the therapeutic agent of at least one of the at least one ormore drug eluting components includes a steroid. In another embodiment,the steroid is an angiostatic steroid. In one embodiment, thetherapeutic agent of at least one of the at least one or more drugeluting components includes an anti-inflammatory drug. In oneembodiment, the therapeutic agent of at least one of the at least one ormore drug eluting components includes an anti-proliferative compound. Inone embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes an antimycotic compound. Inone embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes an antimitotic compound. Inone embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes an antimetabolite compound.In one embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes a pain-relieving drug. Inone embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes a corticosteroid. In oneembodiment, the therapeutic agent of at least one of the at least one ormore drug eluting components includes a non-steroidal anti-inflammatoryagent. In one embodiment, the therapeutic agent of at least one of theat least one or more drug eluting components includes a co-drug. In oneembodiment, the therapeutic agent of at least one of the at least one ormore drug eluting components includes a growth factor. In oneembodiment, the growth factor includes bone morphogenetic protein 2. Inone embodiment, the therapeutic agent of at least one of the at leastone or more drug eluting components includes a local anesthetic. In oneembodiment, the local anesthetic includes lidocaine.

In one embodiment, the reservoir region is shaped and dimensioned toretain the at least one or more drug eluting components when the atleast one or more drug eluting components are in a cured condition.

In one embodiment, the drug eluting surgical screw further includes alip configured and dimensioned to retain the drug eluting component whenthe at least one or more drug eluting components are in a curedcondition.

In one embodiment, the drug eluting surgical screw further includes atleast two drug eluting components.

In one embodiment, the present invention is a method of manufacturing adrug eluting surgical screw, said method including mixing a drug elutingcomponent with a solvent to form a solution, the drug eluting componentincluding a carrier matrix and a therapeutic agent, the therapeuticagent being at least about 20 wt % of the drug eluting component priorto any implantation of the drug eluting surgical screw; heating thesolution to evaporate the solvent and form a film; configuring at leasta portion of the film to a size and shape that complements a driverecess of a surgical screw; placing the at least a portion of the filminto the drive recess of the surgical screw; heating the at least aportion of the film to conform to the size and shape of a cross-sectionof the drive recess; and pressing the at least a portion of the heatedfilm into the drive recess with a forming tool. A forming tool ispreferably used to apply sufficient pressure to the heated film tocreate a bond between the film and the surgical screw.

In one embodiment, the present invention is a method of manufacturing adrug eluting surgical screw, said method including compounding a drugeluting component, the drug eluting component including a carrier matrixand a therapeutic agent, the therapeutic agent being at least about 20wt % of the drug eluting component prior to any implantation of the drugeluting surgical screw; extruding the compounded drug eluting componentto form a film; configuring at least a portion of the film to a size andshape that complements a drive recess of a surgical screw; placing theat least a portion of the film into the drive recess of the surgicalscrew; heating the at least a portion of the film to conform to the sizeand shape of a cross-section of the drive recess; and pressing the atleast a portion of the heated film into the drive recess with a formingtool.

In one embodiment, the present invention is a method of manufacturing adrug eluting surgical screw, said method including compounding a drugeluting component, the drug eluting component including a carrier matrixand a therapeutic agent, the therapeutic agent being at least about 20wt % of the drug eluting component prior to any implantation of the drugeluting surgical screw; compression molding the compounded drug elutingcomponent to form a film; configuring at least a portion of the film toa size and shape that complements a drive recess of a surgical screw;placing the at least a portion of the film into the drive recess of thesurgical screw; heating the at least a portion of the film to conform tothe size and shape of a cross-section of the drive recess; and pressingthe at least a portion of the heated film into the drive recess with aforming tool.

In one embodiment, each step is repeated sequentially to add anadditional drug eluting component to the drive recess of the surgicalscrew.

In one embodiment, the drug eluting component is configured to elute atleast about 80% of the therapeutic agent over a three day periodstarting from when the drug eluting surgical screw is implanted into ananimal.

In one embodiment, the concentration of the therapeutic agent is betweenabout 20 wt % and about 60 wt % of the drug eluting component prior toany implantation of the drug eluting surgical screw.

In one embodiment, the concentration of the therapeutic agent is betweenabout 20 wt % and about 40 wt % of the drug eluting component prior toany implantation of the drug eluting surgical screw.

In one embodiment, the carrier matrix includes a bioabsorbable polymer.In one embodiment, the bioabsorbable polymer includes polycaprolactone,polylactic acid, polyglycolic acid, polyethylene glycol, or acombination thereof. In one embodiment, the carrier matrix includespolyethylene glycol, polyvinyl alcohol, glycerine, salts or a watersoluble crystalline solid. In one embodiment, the carrier matrixincludes silica, hydroxyapatite, calcium phosphate, bioglass or acombination thereof. In one embodiment, the carrier matrix includes ahydrophobic bioabsorbable polymer. In one embodiment, the hydrophobicbioabsorbable polymer includes a water swellable additive which swellswith water after implantation into the body. In one embodiment, thecarrier matrix includes a nonabsorbable polymer. In another embodiment,the nonabsorbable polymer includes poly(methyl methacrylate). In oneembodiment, the carrier matrix includes a nonabsorbable polymer and abioabsorbable polymer. In one embodiment, the bioabsorbable polymerincludes polycaprolactone, polylactic acid, polyglycolic acid,polyethylene glycol, or a combination thereof. In one embodiment, thebioabsorbable polymer includes an erodible ceramic. In one embodiment,the bioabsorbable polymer includes a biostable ceramic. In oneembodiment, the bioabsorbable polymer includes a natural biopolymer. Inanother embodiment, the natural biopolymer includes gelatin, alginates,chitosan, collagen or hyaluronate.

In one embodiment, the drug eluting component includes a nonabsorbablepolymer and a soluble additive. In one embodiment, the nonabsorbablepolymer includes poly(methyl methacrylate). In one embodiment, thesoluble additive includes polyethylene glycol, polyvinyl alcohol,glycerine, salts or a water soluble crystalline solid.

In one embodiment, the drug eluting component includes a concentrationgradient.

In one embodiment, the therapeutic agent includes gentamicin. In anotherembodiment, the therapeutic agent includes a steroid. In one embodiment,the steroid is an angiostatic steroid. In one embodiment, thetherapeutic agent includes an anti-inflammatory drug. In one embodiment,the therapeutic agent includes an anti-proliferative compound. In oneembodiment, the therapeutic agent includes an antimycotic compound. Inone embodiment, the therapeutic agent includes an antimitotic compound.In one embodiment, the therapeutic agent includes an antimetabolitecompound. In one embodiment, the therapeutic agent includes apain-relieving drug. In one embodiment, the therapeutic agent includes acorticosteroid. In one embodiment, the therapeutic agent includes anon-steroidal anti-inflammatory agent. In one embodiment, thetherapeutic agent includes a co-drug. In one embodiment, the therapeuticagent includes a growth factor. In one embodiment, the growth factorincludes bone morphogenetic protein 2. In another embodiment, thetherapeutic agent includes a local anesthetic. In one embodiment, thelocal anesthetic includes lidocaine.

One embodiment of the present invention is drug eluting surgical screwincluding a shaft having a threaded portion; a head having a driverecess disposed at a proximal end of the shaft, the drive recess havinga reservoir region and a driver engagement region; and a drug elutingcomponent disposed within the reservoir region of the drive recess in amanner that does not substantially impair a connection between a driverand the surgical screw when the driver is operably disposed within thedriver engagement region, the drug eluting component including a carriermatrix and a therapeutic agent, the therapeutic agent being at leastabout 20 wt % of the drug eluting component prior to any implantation ofthe drug eluting surgical screw.

In one embodiment, the drug eluting component is configured to elute atleast about 80% of the therapeutic agent over a three day periodstarting from when the drug eluting surgical screw is implanted into ananimal. In another embodiment, the concentration of the therapeuticagent between about 20 wt % and about 60 wt % of the drug elutingcomponent prior to any implantation of the drug eluting surgical screw.In another embodiment, the concentration of the therapeutic agent isbetween about 20 wt % and about 40 wt % of the drug eluting componentprior to any implantation of the drug eluting surgical screw.

In one embodiment, the reservoir region defines a reservoir volume, thedrive recess defines a drive recess volume and the reservoir volume isfrom about 10% to about 12% of the drive recess volume.

In another embodiment, the reservoir region of the drive recess isadjacent to the driver engagement region and the drug eluting componentdoes not extend into the driver engagement region.

In certain embodiments, the carrier matrix includes polycaprolactone,polylactic acid, polyglycolic acid, polyethylene glycol, or acombination thereof.

In one embodiment, the therapeutic agent includes gentamicin.

In other embodiments, the reservoir region is shaped and dimensioned toretain the drug eluting component when the drug eluting component is ina cured condition.

In another embodiment, the drug eluting surgical screw further includesa lip configured and dimensioned to retain the drug eluting componentwhen the drug eluting component is in a cured condition.

In one embodiment, the invention is directed to a method ofmanufacturing a drug eluting surgical screw, the method including mixinga drug eluting component with a solvent to form a solution, the drugeluting component including a carrier matrix and a therapeutic agent,the therapeutic agent being at least about 20 wt % of the drug elutingcomponent prior to any implantation of the drug eluting surgical screw;heating the solution to evaporate the solvent and form a film;configuring at least a portion of the film to a size and shape thatcomplements a drive recess of a surgical screw; placing the at least aportion of the film into the drive recess of the surgical screw; heatingthe at least a portion of the film to conform to the size and shape of across-section of the drive recess; and pressing the at least a portionof the heated film into the drive recess. A forming tool is preferablyused to apply sufficient pressure to the heated film to create a bondbetween the film and the surgical screw.

In one embodiment, the drug eluting component is configured to elute atleast about 80% of the therapeutic agent over a three day periodstarting from when the drug eluting surgical screw is implanted into ananimal. In another embodiment, the therapeutic agent is from about 20 wt% to about 60 wt % of the drug eluting component prior to anyimplantation of the drug eluting surgical screw. In another embodiment,the concentration of the therapeutic agent is between about 20 wt % andabout 40 wt % of the drug eluting component prior to any implantation ofthe drug eluting surgical screw.

In one embodiment, the carrier matrix includes polycaprolactone,polylactic acid, polyglycolic acid, polyethylene glycol, or acombination thereof.

In certain embodiments, the therapeutic agent includes gentamicin.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The foregoing summary, as well as the following detailed description ofembodiments of the present invention, will be better understood whenread in conjunction with the appended drawings of exemplary embodiments.It should be understood, however, that the invention is not limited tothe precise arrangements and instrumentalities shown.

In the drawings:

FIG. 1A is a top view and FIG. 1B is a side perspective partialcross-sectional view of a surgical screw according to one embodiment;

FIG. 2A is a top view and FIG. 2B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having a drugeluting matrix in the drive recess;

FIG. 3A is a top view and FIG. 3B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having a drugeluting matrix in the drive recess with a diffusion barrier layer;

FIG. 4A is a top view and FIG. 4B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having twolayers of drug eluting matrix in the drive recess, containing twodifferent drugs;

FIG. 5A is a top view and FIG. 5B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having a drugeluting matrix in the drive recess with a graded drug concentration;

FIG. 6A is a top view and FIG. 6B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having anadditional reservoir added to the bottom of the drive recess and havinga drug eluting matrix in the drive recess; and

FIG. 7A is a top view and FIG. 7B is a side perspective partialcross-sectional view of an embodiment of a surgical screw having a lipconfigured and dimensioned to retain a drug eluting component when thedrug eluting component is in a cured condition.

DETAILED DESCRIPTION OF THE INVENTION

With reference to the accompanying drawings, various embodiments of thepresent invention are described more fully below. Some but not allembodiments of the present invention are shown. Indeed, variousembodiments of the invention may be embodied in many different forms andshould not be construed as limited to the embodiments expresslydescribed. Like numbers refer to like elements throughout. The singularforms “a,” “an,” and “the” include the singular and plural unless thecontext clearly dictates otherwise.

As shown generally in FIGS. 1A-7B, embodiments of the present inventionare directed toward a surgical screw 100. In some embodiments, thesurgical screw has a shaft 110. In one embodiment, the shaft 110 has athreaded portion 120. In certain embodiments, surgical screw 100includes a head 140 disposed at a proximal end 130 of the shaft 110. Inone embodiment, the head 140 has a drive recess 150. In one embodiment,the drive recess 150 is hexagonally shaped. Although illustrated asbeing hexagonally shaped, it is envisioned that the shape of the driverecess 150 may be configured in any manner suitable for distributing aninsertion force throughout the screw, e.g., other polygonal or generallypolygonal shapes, semi-circular, slotted, cross-recessed, torx star, ormultiple round holes.

Referring to FIG. 2B, the drive recess 150, in certain embodiments, hasa reservoir region 160 and a driver engagement region 170. As seen bycomparing FIGS. 2B and 6B, in certain embodiments, the reservoir region160 can be of varied shape and depth. The reservoir region 160 can beany region of the head 140 of the screw 100 that can be coated with adrug eluting component 200 in a manner that will not substantiallyimpair a connection between a driver and the surgical screw 100 when thedriver is operably disposed within the driver engagement region 170. Thedriver engagement region 170 can be any region of the head 140 of thescrew 100, either coated or uncoated with the drug eluting component200, that is engageable with a driver when the driver is operablydisposed within the head 140. The reservoir region 160 and driverengagement region 170 need not be exclusive and may overlap.

In one embodiment, the reservoir region 160 defines a reservoir volume210, the drive recess 150 defines a driver recess volume 220 and thereservoir volume 210 is from about 10% to about 12% of the driver recessvolume. In other embodiments, the reservoir volume 210 is about 8%,about 8.5%, about 9%, about 9.5%, about 10%, about 10.5%, about 11%,about 11.5%, about 12%, about 12.5%, about 13%, about 13.5%, about 14%or any range determinable from the preceding percents (for example,about 8% to about 9.5% or about 8.5% to about 13%) of the driver recessvolume 220.

In certain embodiments, multiple layers of drug eluting components canbe layered into the reservoir region 160 of the drive recess 150 toallow for multiple therapeutic agents to be released at different rates,sequentially, or simultaneously in different concentrations. One of thelayers may not contain a therapeutic agent, but serve as a barrier layerto inhibit diffusion of the drug. Exemplary materials which could act asa barrier layer include bioabsorbable polymers such as polycaprolactoneor polyglycolide, natural fatty acids such as palmitic acid or stearicacid, and natural biopolymers such as collagen or alginate.

As shown in FIG. 3B, in one embodiment, both a diffusion barrier layer300 and a drug eluting component 200 are disposed within the reservoirregion 160 of the drive recess 150.

Further, FIG. 4B illustrates an exemplary view of the surgical screwwhere two drug eluting components, drug eluting component 200 and drugeluting component 400, are disposed within the reservoir region 160 ofthe drive recess 150. In some embodiments, drug eluting component 200and drug eluting component 400 include different therapeutic agents. Inother embodiments, the drug eluting component 200 and drug elutingcomponent 400 are configured to elute a therapeutic agent at differingrelease rates.

FIG. 5B shows an exemplary embodiment of the invention having a drugeluting component with a graded concentration 500, e.g., a therapeuticagent being less concentrated at the surface and gradually moreconcentrated at deeper depths or, alternatively, a therapeutic agentbeing more concentrated at the surface and gradually less concentratedat deeper depths.

As shown generally in FIG. 2B, one embodiment of the present inventionincludes a drug eluting component 200 disposed within the reservoirregion 160 of the drive recess 150. In certain embodiments, the drugeluting component 200 is positioned in a manner so that it does notsubstantially impair a connection between a driver and the surgicalscrew 100 when the driver is operably disposed within the driverengagement region 170. For example, as shown in FIG. 2B, the drugeluting component 200 may be positioned at the base 230 of the head 140.In other embodiments, the reservoir region 160 of the drive recess 150is adjacent to the driver engagement region 170 and the drug elutingcomponent 200 does not extend into the driver engagement region 170.

In one embodiment, the reservoir region 160 is shaped and dimensioned toretain the drug eluting component 200 when the drug eluting component200 is in a cured condition. For example, as shown in FIGS. 7A and 7B,the surgical screw 100 includes a lip 700 configured and dimensioned toretain the drug eluting component 200 when the drug eluting component200 is in a cured condition.

In one embodiment, the drug eluting component 200 includes a carriermatrix containing a therapeutic agent. In certain embodiments, thecarrier matrix includes a material that facilitates the release rate ofthe therapeutic agent into the body, e.g., a polymer, ceramic, orhydrogel. In one embodiment, the carrier matrix includes a bioabsorbablepolymer, e.g., polycaprolactone, polylactic acid, polyglycolic acid,polyethylene glycol, or a combination thereof.

In other embodiments, the carrier matrix includes a soluble additivewhich dissolves at a controlled rate, generating pores through which thetherapeutic agent can elute. Examples of a soluble additive wouldinclude polyethylene glycol, polyvinyl alcohol, glycerine, salts orwater soluble crystalline solids. By varying the amount of solubleadditive, the elution rate of the therapeutic agent may be modified.Certain embodiments having differing release rates, can be achieved byhaving multiple drug eluting components, each having differingbioabsorbable matrices having differing soluble additives.

In another embodiment, the carrier matrix includes a hydrophobicbioabsorbable polymer that contains a water swellable additive thatswells with water after implantation into the body, allowing thetherapeutic agent to be released at an increased rate. By varying theamount of water swellable additive, the elution rate of the therapeuticagent may be modified.

In one embodiment, the carrier matrix includes a nonabsorbable polymer,e.g., poly(methyl methacrylate).

In another embodiment, the carrier matrix includes a nonabsorbablepolymer and a soluble additive, e.g., polyethylene glycol, polyvinylalcohol, glycerine, salts or water soluble crystalline solids. Thesoluble additive dissolves at a controlled rate, generating pores in thenonabsorbable matrix through which a therapeutic agent can elute.

In certain embodiments, the carrier matrix includes a blend ofbioabsorbable polymer and nonabsorbable polymer.

In other embodiments, the carrier matrix includes an erodible orbiostable ceramic, e.g., silica, hydroxyapatite, calcium phosphate,bioglass, or a combination thereof.

In one embodiment, the carrier matrix includes a natural biopolymer,e.g., gelatin, alginates, chitosan, collagen or hyaluronate.

In one embodiment, the therapeutic agent includes an antibiotic or acombination of multiple antibiotics. In one embodiment, the therapeuticagent includes gentamicin.

In other embodiments, the therapeutic agent includes steroids,anti-inflammatory drugs, anti-proliferative compounds, antimycoticcompounds, an antimitotic compounds, antimetabolite compounds,pain-relieving drugs, corticosteroids, angiostatic steroids,non-steroidal anti-inflammatory agents, and/or co-drugs.

In certain embodiments, the therapeutic agent includes a growth factor,e.g., bone morphogenetic protein 2 (BMP-2). In other embodiments, thetherapeutic agent includes a local anesthetic, e.g., lidocaine.

The therapeutic agent, in certain embodiments, can either be dissolvedcompletely into the material that facilitates its release into the bodyor remain as discrete particles within that material.

In one embodiment, the therapeutic agent constitutes at least about 20wt % of the drug eluting component prior to any implantation of the drugeluting surgical screw 100. In one embodiment, the therapeutic agentconstitutes between about 20 wt % and about 60 wt % of the drug elutingcomponent prior to any implantation of the drug eluting surgical screw100. In one embodiment, the therapeutic agent constitutes between about20 wt % and about 40 wt % of the drug eluting component prior to anyimplantation of the drug eluting surgical screw 100. In otherembodiments, the therapeutic agent constitutes about 20 wt %, about 21wt %, about 22 wt %, about 23 wt %, about 24 wt %, about 25 wt %, about26 wt %, about 27 wt %, about 28 wt %, about 29 wt %, about 30 wt %,about 31 wt %, about 32 wt %, about 33 wt %, about 34 wt %, about 35 wt%, about 36 wt %, about 37 wt %, about 38 wt %, about 39 wt %, about 40wt %, about 41 wt %, about 42 wt %, about 43 wt %, about 44 wt %, about45 wt %, about 46 wt %, about 47 wt %, about 48 wt %, about 49 wt %,about 50 wt %, about 51 wt %, about 52 wt %, about 53 wt %, about 54 wt%, about 55 wt %, about 56 wt %, about 57 wt %, about 58 wt %, about 59wt %, about 60 wt % or any range determinable from the preceding weightpercents (for example, about 51 wt % to about 55 wt % or about 30 wt %to about 52 wt %) of the drug eluting component prior to anyimplantation of the drug eluting surgical screw 100.

In one embodiment, the drug eluting component 200 is configured to eluteat least about 80% of the therapeutic agent over a three day periodstarting from when the drug eluting surgical screw 100 is implanted intothe animal. In other embodiments, the drug eluting component 200 isconfigured to elute about 50%, about 51%, about 52%, about 53%, about54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%,about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about67%, about 68%, about 69%, about 70%, about 71%, about 72%, about 73%,about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%,about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%,about 100% or any range determinable from the preceding percents (forexample, about 50% to about 77% or about 85% to about 94%) of thetherapeutic agent over a one day, two day, three day, four day, fiveday, six day, seven day or any range determinable from the precedingdays (for example, 1-3 days or 3-4 days) period starting from when thedrug eluting surgical screw 100 is implanted into the animal.

In one embodiment, the present invention includes a method ofmanufacturing a drug eluting surgical screw 100. In one embodiment, themethod includes forming a film derived from a drug eluting component. Inone embodiment, a film is formed by mixing a drug eluting component witha solvent to form a solution and heating the solution to evaporate thesolvent and form a film. In another embodiment, a film is formed bysubjecting a drug eluting component to a melting process, e.g., by aprocess including compounding, and then subjecting the melted drugeluting component to extrusion or compression molding. In oneembodiment, after the film has been formed, the method includes,configuring at least a portion of the film to a size and shape thatcomplements a drive recess of a surgical screw. In one embodiment, themethod further includes placing the at least a portion of the film intothe drive recess 150 of the surgical screw 100. In one embodiment, afterplacing the at least a portion of the film into the drive recess 150,heating the at least a portion of the film to conform to the size andshape of a cross-section of the drive recess. In one embodiment, afterheating the at least a portion of the film, the method includes,pressing the at least a portion of the heated film into the drive recess150. In one embodiment, a forming tool, e.g., a screwdriver with an endshaped to fit within the drive recess, is used, e.g., used by pressingthe heated film into the drive recess 150, to form a sufficient bondbetween the at least a portion of the heated film and the drive recessside walls.

In one embodiment, the method of manufacturing a drug eluting surgicalscrew 100 described above is repeated to create a drug eluting surgicalscrew 100 having multiple layers of drug eluting components, e.g., asshown in FIGS. 4A and 4B.

In one embodiment, the present invention includes a method of using thedrug eluting surgical screw 100 to secure an implant, e.g., a fixationplate. In one embodiment, the method includes forming a cavity in a bonefor receiving the drug eluting screw 100, e.g., via drilling. The methodfurther may include placing an implant having an aperture against thebone, the aperture being aligned with the cavity. The method further mayinclude using a driver to fix the drug eluting screw 100 to the bone,whereby the implant is held between the bone and the head of the screw.

In one embodiment, the present invention includes a method of reducingthe risk of infection following surgery. In one embodiment, the methodincludes using the drug eluting surgical screw 100 to secure an implantin an animal following surgery. In certain embodiments, the drug elutingcomponent 200 will elute an antibiotic, e.g., gentamicin, locally at thesurface of the implant thereby reducing the risk of infection.

It will be appreciated by those skilled in the art that changes could bemade to the exemplary embodiments shown and described above withoutdeparting from the broad inventive concept thereof. It is understood,therefore, that this invention is not limited to the exemplaryembodiments shown and described, but it is intended to covermodifications within the spirit and scope of the present invention asdefined by the claims. For example, specific features of the exemplaryembodiments may or may not be part of the claimed invention and featuresof the disclosed embodiments may be combined.

It is to be understood that at least some of the figures anddescriptions of the invention have been simplified to focus on elementsthat are relevant for a clear understanding of the invention, whileeliminating, for purposes of clarity, other elements that those ofordinary skill in the art will appreciate may also comprise a portion ofthe invention. However, because such elements are well known in the art,and because they do not necessarily facilitate a better understanding ofthe invention, a description of such elements is not provided herein.

Further, to the extent that the method does not rely on the particularorder of steps set forth herein, the particular order of the stepsshould not be construed as limitation on the claims. The claims directedto the method of the present invention should not be limited to theperformance of their steps in the order written, and one skilled in theart can readily appreciate that the steps may be varied and still remainwithin the spirit and scope of the present invention.

What is claimed is:
 1. A drug eluting surgical screw comprising a shafthaving a threaded portion; a head having a drive recess disposed at aproximal end of the shaft, the drive recess having a reservoir regionand a driver engagement region; and a drug eluting film disposed withinthe reservoir region of the drive recess in a manner that does notsubstantially impair a connection between a driver and the surgicalscrew when the driver is operably disposed within the driver engagementregion, wherein the drug eluting film comprises a mixture of a carriermatrix and a therapeutic agent, the therapeutic agent being at least 20wt. % of the drug eluting film, prior to any implantation of the drugeluting surgical screw; and, wherein the drug eluting film includes aconcentration gradient of the therapeutic agent within the film from adirection at a surface of the film through the depth of the film.
 2. Thedrug eluting surgical screw of claim 1, wherein the concentration of thetherapeutic agent of the drug eluting film is between 20 wt. % and 60wt. % of the drug eluting film prior to any implantation of the drugeluting surgical screw.
 3. The drug eluting surgical screw of claim 2,wherein the concentration of the therapeutic agent of the drug elutingfilm is between 20 wt. % and 40 wt. % of the drug eluting film prior toany implantation of the drug eluting surgical screw.
 4. The drug elutingsurgical screw of claim 1, wherein the drug eluting film is configuredto elute at least 80% of its therapeutic agent over a three day periodstarting from when the drug eluting surgical screw is implanted into ananimal.
 5. The drug eluting surgical screw of claim 1, wherein thereservoir region defines a reservoir volume, the drive recess defines adrive recess volume and the reservoir volume is from 10% to 12% of thedrive recess volume.
 6. The drug eluting surgical screw of claim 1,wherein the reservoir region of the drive recess is adjacent to thedriver engagement region and the drug eluting film does not extend intothe driver engagement region.
 7. The drug eluting surgical screw ofclaim 1, wherein the carrier matrix of the drug eluting film includes abioabsorbable polymer.
 8. The drug eluting surgical screw of claim 7,wherein the bioabsorbable polymer includes polycaprolactone, polylacticacid, polyglycolic acid, polyethylene glycol, or a combination thereof.9. The drug eluting surgical screw of claim 1, wherein the carriermatrix of the drug eluting film includes polyethylene glycol, polyvinylalcohol, glycerine, salts or a water soluble crystalline solid.
 10. Thedrug eluting surgical screw of claim 1, wherein the carrier matrix ofthe drug eluting film includes silica, hydroxyapatite, calciumphosphate, bioglass or a combination thereof.
 11. The drug elutingsurgical screw of claim 1, wherein the carrier matrix of the drugeluting film includes a hydrophobic bioabsorbable polymer.
 12. The drugeluting surgical screw of claim 1, wherein the carrier matrix of thedrug eluting film includes a nonabsorbable polymer.
 13. The drug elutingsurgical screw of claim 1, wherein the carrier matrix of the drugeluting film includes a nonabsorbable polymer and a bioabsorbablepolymer.
 14. The drug eluting surgical screw of claim 1, wherein thecarrier matrix of the drug eluting film includes an erodible ceramic ora biostable ceramic.
 15. The drug eluting surgical screw of claim 1,wherein the carrier matrix of the drug eluting film includes anonabsorbable polymer and a soluble additive.
 16. The drug elutingsurgical screw of claim 1, wherein the therapeutic agent of the drugeluting film includes gentamicin.
 17. The drug eluting surgical screw ofclaim 1, further comprising a lip configured and dimensioned to retainthe drug eluting film within the reservoir region.
 18. The drug elutingsurgical screw of claim 1, further comprising at least two drug elutingfilms.
 19. The drug eluting surgical screw of claim 1, wherein the shapeof the drive recess is generally polygonal.
 20. The drug elutingsurgical screw of claim 19, wherein the shape of the drive recess ishexagonal or star shaped.
 21. The drug eluting surgical screw of claim1, wherein the drug eluting film is bonded to the screw.
 22. The drugeluting surgical screw of claim 1, wherein the therapeutic agent is atleast freely soluble in water.
 23. The drug eluting screw of claim 1,wherein the drug eluting film elutes at least 50% of the therapeuticagent within 2 days starting from when the drug eluting screw isimplanted into an animal.
 24. The drug eluting screw of claim 1, whereinthe drug eluting film elutes at least 75% of the therapeutic agentwithin 7 days starting from when the drug eluting screw is implantedinto an animal.